crossing96/oncoscreening huggingface dataset:
Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy.	Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics.	bladder
The Feasibility and Utility of Cystoscopy-Guided Hydrogel Marker Placement in Patients With Muscle-Invasive Bladder Cancer.	PURPOSE: Fiducial markers at the borders of bladder tumors are useful to facilitate target delineation radiation therapy (RT) and offer the possibility of image guided RT for a focal boost. Our purpose was to evaluate the feasibility and technical performance of cystoscopy-guided placement of hydrogel markers in patients with bladder cancer referred for RT. METHODS AND MATERIALS: Ours was a prospective, multicenter, feasibility, and utility study. Thirty-two consecutive patients with muscle-invasive bladder cancer, referred for RT, underwent cystoscopy-guided implantation of hydrogel markers. Feasibility, clinical performance of the markers, and adverse events were registered. Computer tomography (CT) scans and cone beam CT (CBCT) scans acquired during RT were analyzed to evaluate the visibility and stability of the markers during the radiation period. RESULTS: A total of 107 hydrogel spots were implanted in 32 patients with bladder cancer. There were no procedure-related adverse events. On the simulation CT scan 76.6% of the implanted markers were sufficient for tumor delineation. At start of treatment 52.3% were visible on the CBCT and adequate for positional verification on a routine basis. The washout rate during treatment was 9.3%. At the end of treatment 46.7% of implanted spots were visible on CBCT scan and adequate for routine positional verification. At patient level, in 31.2% of cases, use of hydrogel fiducials showed adequate performance throughout the whole course. CONCLUSIONS: Cystoscopy-guided placement of hydrogel markers is both safe and feasible for muscle-invasive bladder tumors. Adequate performance for radiation purposes throughout the whole course (implantation, delineation, and positional verification) was 46.7% of all implanted markers, leaving room for improvement.	bladder
Perivascular Epithelioid Cell Tumor of the Urinary Bladder: A Systematic Review.	Perivascular epithelioid cell tumor (PEComa) of the urinary bladder is a rare neoplasm showing distinct melanocytic and smooth muscle differentiation. We aimed to review the clinicopathologic features of bladder PEComa using all the available cases in the literature, along with 2 new cases from our database. The patients included 15 females and 15 males with a mean age of 39.2 ± 15.3 years. Painless hematuria was the most common clinical presentation. The tumors were usually well circumscribed with a mean tumor size of 4.4 ± 2.7 cm. Bladder PEComas demonstrated nests, trabeculae, or sheets of epithelioid cells with intermixed spindled cells and numerous thin-walled vessels. Immunohistochemical studies showed that the tumors were positive for HMB45 (27/27), cathepsin (4/4), SMA (20/22), and caldesmon (3/3) and were negative for pan cytokeratin (0/18) and EMA (0/4). Molecular studies revealed that PEComa was associated with the TFE3 (n = 3) and EWSR1 (n = 1) gene rearrangements. Treatment included partial cystectomy (n = 18), transurethral resection (n = 8), and radical cystectomy (n = 4). Twenty patients had no evidence of disease during a mean follow-up time of 19.4 ± 17.2 months. Two patients had recurrence, and 1 patient died of metastatic disease. In conclusion, bladder PEComas demonstrate distinct morphologic and immunohistochemical features. Although most tumors follow a benign course, a small subset may develop metastasis and cause death.	bladder
Urinary tract infections and risk of squamous cell carcinoma bladder cancer: A Danish nationwide case-control study.	Schistosoma haematobium infection can lead to squamous cell carcinomas (SCC) of the bladder. Whether this also applies to more common urinary tract infections (UTIs) is unclear. We therefore aimed to investigate the association between UTIs, reflected by the use of specific antibiotics and risk of SCC of the bladder. We conducted a Danish nationwide case-control study and identified histologically verified bladder cancer cases (2000-2015; n = 12,271) and age- and sex-matched cancer-free controls. We computed odds ratios (ORs) with 95% confidence intervals (CI) associating the use of UTI-specific antibiotics with SCC bladder cancer, using conditional logistic regression. We applied a 2-year lag-time to minimize reverse causation. To aid interpretation, similar analyses were performed for other bladder cancer types and other antibiotics. We identified 333 SCC cases (2.7% of all bladder cancers). Compared to no use (0-1 prescription), high-use (≥10 prescriptions) of UTI-specific antibiotics was associated with SCC with an OR of 11.4 (CI 7.6-17.2) and a clear dose-response pattern (p(trend) < 0.001). Use of phenoxymethylpenicillin, an antibiotic not used against UTIs, was not associated with SCC after adjustment for use of UTI-specific antibiotics (OR 0.5). Furthermore, UTI-specific antibiotic use was not associated with urothelial carcinomas (n = 11,029; OR 1.13; CI 0.97-1.32). Excluding patients with known urogenital disease did not influence the SCC estimates (overall OR 10.8; CI 6.2-18.9). Data on smoking were lacking, however, a quantitative bias analysis suggested this to be of limited importance. In conclusion, common UTIs are strong, dose-dependent and specifically associated with risk of SCC of the bladder.	bladder
Characterization of a learning curve for robotic cystectomy with intracorporeal urinary diversion at two institutions using the cumulative sum (CUSUM) method.	INTRODUCTION: Robotic cystectomy with intracorporeal urinary diversion (RCID) is a technically challenging procedure. It is understood that this approach has a learning curve; however, limited studies have characterized this learning curve. The cumulative sum (CUSUM) method plots the learning curve. The aim of this study was to use the CUSUM approach to investigate the number of cases required to reach a consistent, desired performance level for RCID. MATERIALS AND METHODS: Retrospective study of the first 27 and 28 RCID cases performed by two new fellowship trained faculty at two separate institutions from November 2014 to January 2018. Total operating time was calculated and the CUSUM method was used to describe the learning curve, the number of cases needed for a consistent performance level. RESULTS: Twenty-seven and 28 patients were reviewed from two institutions (A and B), with 8 and 7 females, 19 and 21 males and an average age of 66.7 and 67.6 years, respectively. Twelve and ten cases, respectively, had final pathology of stage T3 bladder cancer or higher. The CUSUM curve demonstrated a learning curve of 10 and 11 cases, respectively, when the curve transitioned from steady improvement in OR times (upward slope of curve) to a relative steady state of OR times (plateau of curve). The average lymph node yield, rate of ureteral stricture, and positive margins were also examined with no learning curve noted. CONCLUSION: In RCID, approximately 10 cases were required by robotically trained new faculty to reach a steady-state level of performance.	bladder
[Renal transplantation in urinary diversions].	Renal transplantations in augmented bladders or urinary diversions are rare, accounting for only 1-2% of all renal transplantations. In most cases a dysfunctional lower urinary tract is the cause of end-stage renal disease in these patients; therefore recovery of the lower urinary tract is mandatory for long-term graft survival. Usually, urinary diversion is timed several months prior to renal transplantation. Beside renal transplantations into an ileum conduit, renal transplantations in continent urinary diversions have become increasingly popular. The most frequent complications are bacteriuria and urinary tract infections, which usually do not lead to graft loss when treated correctly with antibiotics. Long-term outcome of renal transplantations in urinary diversions is comparable to transplantations in healthy native bladders.	bladder
A Novel Long Non-Coding RNA KMU15 Promotes Growth and Chemoresistance of Bladder Cancer.	BACKGROUND: Chemotherapy constitutes one of the most important adjuvant treatments for bladder cancer. However, many patients usually develop chemoresistance during chemotherapy. At present, lncRNA has been confirmed not only to be involved in tumorigenesis and progression, but also in tumor chemoresistance. However, the relationship between lncRNAs and chemoresistance of bladder cancer have been rarely reported. METHODS: The novel lncRNA-KMU15 was screened by lncRNAs microarray and determination of IC50 in bladder cancer. The expression of KMU15 was evaluated by qRT-PCR. The correlation between KMU15 and clinicopathological parameters was analyzed from clinical cases. The effects of KMU15 on the biological behavior and chemoresistance were investigated by [3H]-TdR incorporation assay and other experiments. The effects of KMU15 on the growth of xenograft tumors and the survival of nude mice under cisplatin were examined in a xenograft mouse model. RESULTS: We confirmed that KMU15 was expressed higher in bladder cancer tissues than paired control tissues. Moreover, the expression of KMU15 was significantly positively correlated with the grade, stage, metastasis, and recurrence of bladder cancer and was significantly negatively correlated with the prognosis. In addition, KMU15 knockdown could significantly inhibit bladder cell proliferation, adhesion, migration, and chemoresistance and promoted apoptosis. Knockdown of KMU15 inhibited the growth of xenografts in nude mice and significantly prolonged the survival of tumor-bearing mice under cisplatin. CONCLUSIONS: The novel lncRNA KMU15, which is highly expressed in bladder cancer tissues, could promote the proliferation and progression and was closely related to the malignant degree of bladder cancer. It could also significantly enhance the chemoresistance of bladder cancer cells. Therefore, it was expected to be a new therapy target for bladder cancer and a potential prognosis biomarker for chemotherapy.	bladder
Tunneling Nanotubes Mediated microRNA-155 Intercellular Transportation Promotes Bladder Cancer Cells' Invasive and Proliferative Capacity.	OBJECTIVE: To investigate differential microRNAs' expression in heterogeneous bladder cancer cells, as well as to investigate the mechanism of changes in invasive and proliferative capacity induced by tunneling nanotubes (TNTs) mediated transport of microRNA between bladder cancer cells of varying histological grade. MATERIALS AND METHODS: Differences in microRNA expression between bladder cancer cells of different grade were identified from a literature review. The identified heterogeneous microRNAs were analyzed by qPCR in T24 (high grade) and RT4 (low grade) bladder cancer cells. Scanning electron microscopy (SEM) and laser confocal fluorescence microscopy (LCM) were used to observe tunneling nanotubes (TNTs) between RT4 and T24 cells. Differentially expressed microRNA was labeled and traced by Fluorescent In Situ Hybridization (FISH) following co-culture of T24 and RT4 cells. MicroRNA mimic and inhibition technologies were applied to investigate how TNTs-mediated intercellular transport of microRNA affects the invasive and proliferative behavior of bladder cancer cells. RESULTS: MicroRNA-155 (miR-155) levels were highly expressed in T24 cells, whereas the same was not true in RT4 cells. MiR-155 was confirmed to be a crucial factor sustaining T24 bladder cancer cell proliferation, migration and cell cycle progression by CCK8, Matrigel test and cell cycle analysis, respectively. After T24 and RT4 co-culture, TNTs were assessed by SEM and LCM between T24 and RT4 cells. In addition, we observed TNTs mediated transport of miR-155 from T24 cells to RT4 cells, which thereby acquired a higher proliferative rate, an increased frequency of cells in the S phase, and increased invasive ability in Matrigel test. At the same time, Deptor, the target protein of miR-155 in RT4 cells, was downregulated, followed by mTOR/4EBP1/p70S6K- eIF4e/S6RP signaling activation. CONCLUSION: MiR-155 was differentially expressed between RT4 and T24 bladder cancer cells. Intercellular transport of miR-155 via TNTs can promote bladder cancer cell reprogramming by Deptor-mTOR signal pathway activation.	bladder
Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors.	BACKGROUND: A rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited. PATIENTS AND METHODS: We included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions. RESULTS: Patients (n = 102) with renal cell carcinoma (RCC) and patients (n = 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P = .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors. CONCLUSION: HPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL.	bladder
[Analysis of influencing factors of ureteral anastomotic stenosis following urinary diversion after laparoscopic radical cystectomy].	Objective: To investigate the influencing factors of ureteroenteric strictures (UES) in patients undergoing laparoscopic radical cystectomy plus urinary diversion (UD). Method: A total of 412 patients who underwent UD after radical prostatectomy from January 2008 to December 2016 were retrospectively included in this study. Age, gender, body mass index (BMI), diversion type, time to diagnosis of UES, duration of ureteral stent, postoperative complications, including urinary tract infections, ureteroenteric leakage and UES were collected. Kaplan-Meier curves were used to describe time to developing UES. Prognostic factors of UES were analyzed using COX proportional hazard regression model. Result: Median follow-up time was 37 (IQR 17-120) months. A total of 59 patients (70 sides) developed UES, including 34 cases on the left side, 14 cases on the right side and 11 cases on both sides, following UD after radical cystectomy. The median time to diagnosis of UES was 7 (IQR 4-11) months. The total incidence of UES was 14.3%. The incidence of UES was 10.9%, 13.3% and 14.1% at 1, 3 and 5 years after UD, respectively. Cox proportional hazard regression model analysis demonstrated that BMI≥25kg·m(-2) (P=0.008), ureteroenteric leakage (P=0.001) and urinary tract infections (P=0.037) were the independent risk factors associated with UES following UD after radical cystectomy. Conclusion: The incidence rate of UES following UD after radical cystectomy was relatively high, which occurs more common on the left side. Obese patients, combined with ureteroenteric leakage, urinary tract infection after UD, are more likely to develop into UES.	bladder
Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules.	BACKGROUND: Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site. MATERIALS AND METHODS: A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI(2.5kD)) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells. RESULTS: Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 µg/mL, whereas the empty and non-targeted formulations did not result any significant cell death. CONCLUSION: These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.	bladder
ENERGIZE: a Phase III study of neoadjuvant chemotherapy alone or with nivolumab with/without linrodostat mesylate for muscle-invasive bladder cancer.	Immune checkpoint inhibitors have revolutionized the treatment of patients with metastatic urothelial carcinoma. In cisplatin-eligible muscle-invasive bladder cancer (MIBC), cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy improves overall survival. Tumor PD-L1 expression increases in MIBC after NAC, suggesting potential synergy in combining PD1/PD-L1 inhibitors with NAC. IDO1 is overexpressed in bladder cancer and is associated with poor outcomes. Linrodostat mesylate (BMS-986205) - a selective, potent, oral IDO1 inhibitor - combined with nivolumab has demonstrated safety and preliminary evidence of clinical activity in metastatic urothelial carcinoma. Here, we discuss the rationale and trial design of the ENERGIZE, a Phase III trial investigating the efficacy of NAC in combination with nivolumab with or without linrodostat followed by postsurgery nivolumab or nivolumab with linrodostat in cisplatin-eligible patients with MIBC. Clinical trial registration number: NCT03661320.	bladder
Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma.	The treatment landscape for locally advanced or metastatic urothelial carcinoma has broadened significantly over recent years. New therapeutic options include immunotherapy with checkpoint inhibitors and targeted therapy with erdafitinib. Despite these advances, gaps remain in the selection and sequencing of optimal therapies. Treatment decisions are often influenced by several patient-specific factors such as tolerability and biomarker expression. Following progression while receiving front- and second-line therapies, there is no widely accepted standard of care for patients. Enrollment into a clinical trial is recommended in all lines of therapy for advanced disease. Antibody-drug conjugates have recently emerged as novel therapeutics allowing for targeted delivery of chemotherapeutic agents. Enfortumab vedotin, a nectin-4-targeted antibody conjugated with monomethyl auristatin E, is the first-in-class therapeutic option and has demonstrated unprecedented response rates following progression on chemotherapy and immunotherapy for advanced disease with a tolerable safety profile. As a result, a biologics license application was submitted to the US FDA in July 2019. Ongoing clinical trials are aiming to further establish the role of enfortumab vedotin in urothelial carcinoma. In this article, we highlight the safety and efficacy of enfortumab vedotin for patients with advanced bladder cancer, ongoing clinical trials, clinical pharmacology, and pharmacokinetics.	bladder